A New 1:1 Drug-Drug Cocrystal of Theophylline and Aspirin: Discovery, Characterization, and Construction of Ternary Phase Diagrams (original) (raw)
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Role of Coformer and Excipient Properties on the Solid-State Stability of Theophylline Cocrystals
Crystal Growth & Design, 2019
The stability of theophylline cocrystals comprised of acidic (glutaric acid), basic (isonicotinamide) or neutral (benzamide) coformers, was evaluated in the presence of several excipients. Tablets of theophylline-glutaric acid (TG) and theophylline-isonicotinamide (TINT) cocrystal were stable 'as is' (no excipient) after storage at °C/75% RH for one week. However, TG and TINT cocrystals dissociated rapidly in the presence of basic and acidic excipients, respectively. The dissociation reaction was water mediated and theophylline, the reaction product, was identified by powder X-ray diffractometry. In case of theophyllinebenzamide (TBZ) cocrystal, storage of tablets with and without excipients at 40 °C/75% RH for one week, resulted in a cocrystal polymorphic transformation. Thus, the potential for excipientinduced cocrystal dissociation exists for cocrystals comprised of acidic and basic coformers. Moreover, if the coformer renders the cocrystal highly water soluble, even in the presence of neutral excipients, there is a propensity for dissociation.
AN OVERVIEW ON PHARMACEUTICAL COCRYSTALS
Padala Alekya*, Jagadeesh Panda, D. Komali, S. Neeraja Sukanya
The cocrystal production and properties are intricate in different ways. It exhibits properties corresponding to dissolution rate, melting point, solubility, chemical stability etc. The crystal engineering has been applied to API’s as an implication to pharmaceutical cocrystal which has been increasingly recognized as an attractive option to polymorph, salts, solvates and crystal habit modifications in dosage form design. Pharmaceutical cocrystals formation has been manifested to influence the solid-state properties (solubility and bioavailability) of poorly water-soluble drugs without compromising its pharmacological activity. To date, there is no agreeable definition, what a cocrystal constitutes. This article intended to presents an overview of pharmaceutical cocrystals with different preparation methods, physicochemical properties and analytical characterization methods. KEY WORDS: cocrystal, API, crystallization, solubility, bioavailability
Pharmaceutical Co-crystal : An Emerging Technique to enhance Physicochemical properties of drugs
International Journal of ChemTech Research, 2020
Major constraints in development of new product are poor aqueous solubility, stability and low oral bioavailability, low permeability. As majority of drugs marketed worldwide are administered by oral route and about 40% -50% of the new molecular entities were never invade into the market because of such biopharmaceutical issues.So issues related to poor physiochemical property of an active pharmaceutical ingredient (API) can be resolved using cocrystallization approach.Crystallization emerge as potential technique for enhancement of solubility of poorly aqueous soluble drugs also helps to improve physicochemical with preserving the pharmacological properties of the API . Cocrystals are solids that are crystalline single-phase materials composed of two or more different molecular and/or ionic compounds generally in a stoichiometric ratio which are neither solvates/hydrates nor simple salts. It is multicomponent system in which one component is API and another is called coformer. Cofo...
International Journal of Pharmaceutics, 2020
The development over the past decade of design strategies for cocrystal preparation have led to numerous methods for the synthesis of cocrystal without take care of their influence on the precise structure and stability of cocrystalline states. On the other hand the mechanism of cocrystal formation remains widely unclear, especially the identification of the type of interactions mostly responsible for the cocrystalline stability. The present study focuses on the influence of the crystalline synthesis method on the polymorphism of cocrystals was analyzed from the preparation of S-ibuprofen/nicotinamide and RS-ibuprofen/nicotinamide cocrystals by co-milling, slow solvent evaporation and crystallization from the melt. X-ray diffraction and Raman spectroscopy experiments have shown that the polymorphic form of the cocrystals obtained by recrystallization from the melt (Form A) is different from that prepared by milling and by slow evaporation in solution (Form B). It was shown that both isothermal and non-isothermal recrystallizations from the melt blending are observed via a transient metastable micro/nano structure of form A. Additionally, it was observed that form A transforms into Form B upon heating via very weak changes in the hydrogen bond network. The crystallization in form A from the melt, instead of form B by other methods, was explained by the difficulty to form a supramolecular organization too far energetically from that existing in the melt. This study shows the crucial role of supramolecular H-bonding on the formation mechanism of cocrystals and how does the synthesis method of cocrystals change the supramolecular organization and the related structure of cocrystals. 2013), administration to the targeted site, or from a regulation point of view (Vippagunta et al., 2001). In this context, the structural information about APIs, including molecular conformation, molecular associations via H-bonding, atomic positions, and stability conditions are required regardless the solid forms of the API, i.e. polymorphs, solvates, hydrates and cocrystals in recent years. Many newly proposed drugs suffer from poor water solubility. Cocrystallization is a growing strategy to overcome the poor dissolution rate of drugs by association with highly water-soluble molecules (Zimmermann and Baranović, 2011). The nature of molecular interaction between APIs and coformers and the synthetic procedures are considered as the main factors involved in the modification of only physicochemical properties without changes in pharmacological properties of APIs. The physicochemical properties of APIs are dependent on the selected conformer. Until now most of works have focused on cocrystal screening and characterization (
2017
The increasing frequency of drugs which have poor aqueous solubility, manufacturability and stability in development offers risk of new drug products with low and variable bioavailability particularly for those drugs administrated by the oral route, with consequences for safety and efficacy. Although number of strategies exists for enhancing the bioavailability of these drugs, newer strategies, dependent on the physical and chemical nature of the molecules are being developed. Crystal engineering approach presents a number of routes such as co-crystallization, polymorphism and salt formation to improve physicochemical properties of drugs, which can be implemented through a detailed knowledge of crystallization processes and the molecular properties of drugs. Pharmaceutical co-crystals are emerging as a new class of solid drugs with improved physicochemical properties, which has attracted increased interests from both industrial and academic researchers. In the present review, the co...
CO-CRYSTALS IN PHARMACEUTICAL SCIENCE: AN UPDATED REVIEW
JETIR, 2023
The concept of Co-crystallization discovered almost a century ago, but it has inspired a great interest of researchers in modern day due to their ability to improve physical properties of pharmaceutical active ingredients. Co-crystallization alters the molecular interactions and composition of pharmaceutical materials, and is considered better alternatives to optimize drug properties. Co-crystallization of a drug with a coformer is an emerging approach to improve the performance of active pharmaceutical ingredients (APIs), such as solubility, dissolution profile, pharmacokinetics and stability. This review article presents a comprehensive overview of pharmaceutical cocrystals, including introduction, historical background, preparation methods, applications & some discovery in Co-crystal field. Furthermore, some examples of drug cocrystals are highlighted to illustrate the effect of crystal structures on the various aspects of active pharmaceutical ingredients, such as solubility, bioavailability, meting point. In this review we have summarized recent discoveries in Co-crystal field and some examples of APIs & their coformer with therapeutic activity in tabular form.
Pharmaceutical Cocrystals—A Review
Proceedings
The design and synthesis of pharmaceutical cocrystals have received great interest in the recent years. Cocrystallization of drug substances offers a tremendous opportunity for the development of new drug products with superior physical and pharmacological properties such as solubility, stability, hydroscopicity, dissolution rates and bioavailability. This short review summarizes this highly topical field, covering why the topic is of interest in pharmaceutical formulation, the definitions and practical scope of cocrystals, cocrystal preparation and characterization, a comparison of different (traditional and novel) methods for cocrystal formation and the implications for regulatory control and intellectual property protection. Traditionally, cocrystals can be prepared by solvent evaporation method, grinding, and slurry method, but every method has its limitations for certain conditions. The current trend for cocrystal formation uses sophisticated methods such as the hot melt extrus...
Pharmaceutical Co-Crystals - Design, Development and Applications
Drug Delivery Letters, 2020
Background: Solubility and dissolution profile are the major factors which directly affect the biological activity of a drug and these factors are governed by the physicochemical properties of the drug. Crystal engineering is a newer and promising approach to improve physicochemical characteristics of a drug without any change in its pharmacological action through a selection of a wide range of easily available crystal formers. Objective: The goal of this review is to summarize the importance of crystal engineering in improving the physicochemical properties of a drug, methods of design, development, and applications of cocrystals along with future trends in research of pharmaceutical co-crystals. Co-crystallization can also be carried out for the molecules which lack ionizable functional groups, unlike salts which require ionizable groups. Conclusion: Co-crystals is an interesting and promising research area amongst pharmaceutical scientists to fine-tune the physicochemical propert...
A Review on Pharmaceutical Cocrystals
2020
Pharmaceutical cocrystals are solid substances and a promising technology which are used to improve the solubility of poor aqueous compounds. They are a very interesting and useful product for improving different properties of drug substances such as dissolution rate, melting point, solubility, chemical stability, etc on the other hand we can say that they are drug pharmacological action modification agents. In the present paper, we review the pharmaceutical co-crystals. Cocrystals are multi-component molecular design allows us to change in the physicochemical properties of solids according to the need, through manipulation of various intermolecular interactions. In this short review, we focus on some recent reports on pharmaceutical co crystals and their emerging subclasses as Charge transfer co-crystals, Energetic co-crystals, and Ternary cocrystals and discuss their methods of characterization and applications of importance in the industrial pharmacy. KeywordCocrystals, solubilit...
Pharmaceutical Co-Crystals: A New Paradigm of Crystal Engineering
A review on pharmaceutical co-crystals, nutraceutical co-crystals and pharmaceutical co-crystal polymorphs depicting their relevance both in academia and pharmaceutical industry because of their potential as new solid forms of the active pharmaceutical ingredient. The overview of crystal engineering to design co-crystals for altered and improved physicochemical properties such as solubility, dissolution rate, bioavailability, hygroscopicity etc., with some examples present in the literature till 2013.